S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells.
- Issue Date
- Nature Publishing Group
- British Journal of Pharmacology (2001) 132, 411-418
- Chlorpromazine ; bradykinin ; phospholipase C ; store-operated Ca2+ entry ; neurotransmitter secretion
- 1 The e ect of chlorpromazine on the store-operated Ca2+ entry activated via the phospholipase C
signalling pathway was investigated in PC12 cells.
2 Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca2+
concentration produced by bradykinin while having no e ect on the initial transient response. The
inhibition was lowered by the removal of extracellular free Ca2+. However, chlorpromazine did not
inhibit bradykinin-induced inositol 1,4,5-trisphosphate production.
3 Chlorpromazine inhibited the bradykinin-induced noradrenaline secretion in a concentration-
dependent manner (IC50: 24+5 mM, n=3).
4 To test for a direct e ect of chlorpromazine on store-operated Ca2+ entry, thapsigargin, an
inhibitor of microsomal Ca2+-ATPase, was used to induce store-operated Ca2+ entry in PC12 cells.
Chlorpromazine reduced the thapsigargin-induced sustained Ca2+ level (IC50: 24+2 mM, n=3), and
the inhibition also occluded the inhibitory action of 1-[-[3-(4-methoxyphenyl) propoxy]-4-
methoxyphenyl]-1H-imidazole hydrochloride (SK&F96365).
5 The results suggest that chlorpromazine negatively modulates the store-operated Ca2+ entry
activated subsequent to PLC activation.
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